Bone disease in thalassemia in the form of low bone mass remains a frequent, debilitating and poorly understood problem, even among well transfused and chelated pre-pubertal and adult patients. In this work we attempted to delineate calcium status and bone mineral density in a group of transfusion dependent thalassemic adolescents of both sexes. Bone mineral density (BMD) at both the lumbar spine and femoral neck was measured in 40 adolescents with beta thalassemia major (TM) by DXA scanning and correlated to biochemical parameters including calcium, phosphorus, alkaline phosphatase, bone alkaline phosphatase, intact parathyroid hormone and 25-OH vitamin D as well as vitamin D receptor (VDR) gene polymorphisms at exon 2 (Fok1). Z-score of BMD at the lumbar spine (-3.3, +/-1.4) was significantly lower than at the femoral neck (-0.68, -/+1.3), (p=0.001). Serum ferritin and VDR genotype were related to BMD only at the femoral neck indicating that the factors determining the BMD at these 2 sites might be different. Seventy-five percent of patients had a low calcium level and hypoparathyroidism was present in 72.5% of patients. The low calcium level was probably caused by a combination of hypoparathyroidism and osteomalacia evidenced by elevated bone alkaline phosphatase presumably resulting from deficient calcium intake. To optimize BMD in TM, it is important to ensure adequate iron chelation and adequate intake of calcium and vitamin D.